There are currently no FDA-approved medications for cocaine addiction. In the previous funding period, several animal models of cocaine abuse were used by this Center to investigate the neuropharmacology of chronic cocaine exposure. The studies described in Project 1 combine three research areas that were separated into distinct Projects in the previous version of the Center (formerly Projects 3, 5 and 6). These studies are designed to systematically investigate in monkeys and rats current medications used clinically to beat cocaine addiction, as well as drugs in the clinical pipeline and drugs that are not approved for human use, but could provide information related to mechanisms of action related to clinical efficacy. Specific Aim 1 will use rhesus monkeys self-administering cocaine to examine the effects of chronic administration of drugs. Treatment drugs that selective decrease cocaine- relative to food-reinforced responding, with no evidence of tolerance or attenuation by higher cocaine doses, will be evaluated in monkey models of cognition (Specific Aim 2). A positive outcome in models of cognition (i.e., improvement in performance) will yield additional studies in experimentally naive monkeys in combination with imaging studies (Projects 2 and 3). Finally, Specific Aim 3 will examine the effects of acute and chronic administration of drug treatments in several rat models of cocaine self-administration. When complete, the studies in this Project will provide basic science information in monkeys and rats across several behavioral endpoints in which different aspects of addiction are modeled, which should be of relevance to clinicians.